Side Effects and Complications Associated with Treating Plutonium Intakes: A Retrospective Review of the Medical Records of LANL Employees Treated for Plutonium Intakes, with Supplementary Interviews.

ABSTRACT: Anecdotal evidence indicates there may be unpublished physical and psychological events associated with the medical treatment of plutonium intakes. A thorough review was conducted of the medical and bioassay records of current and previous Los Alamos National Laboratory (LANL) employees who had experienced plutonium intakes via wound or inhalation. After finding relatively incomplete information in the medical records, the research team interviewed current LANL employees who had undergone chelation therapy and/or surgical excision. Although the dataset is not large enough to reach statistically significant conclusions, it was observed that adverse events associated with treatment appear to be more frequent and more severe than previously reported.

Clinical Therapy of Patients Contaminated with Polonium or Plutonium.

Although most of the harmful radionuclides are of anthropogenic origin and released from military or industrial processes, radioactive substances, such as uranium, also occur naturally in the environment. Low standards of care at nuclear facilities can lead to the contamination of employees with radionuclides due to inhalation of gases or dust or contamination of skin or wounds. Various sources for radionuclide exposure may present concerns for radioactive polonium or plutonium exposure, for instance, terrorist actions on the infrastructure, such as on drinking water basins. Early health effects after extensive radiation exposure may be vomiting, headaches, and fatigue, followed by bone marrow depression, fever, and diarrhea. The main purpose of radionuclide mobilization is to minimize the radiation dose. Since some of the important radionuclides, such as polonium and plutonium, have very long biological half-times after their deposition in bone, liver or kidneys, rapid initiation of chelation treatment is usually imperative after a contamination event. The antidote DMPS (dimercapto-propanesulfonate) is considered the drug of choice for polonium decorporation. DTPA (diethylenetriamine pentaacetate) is a potent chelator especially approved for radionuclide mobilization, including polonium and other actinides. Other chelators and drugs are under investigation as potential chelators of transuranic elements.

Dose Assessment Following a 238Pu-contaminated Wound Case with Chelation and Excision.

The urinary excretion and wound retention data collected after a Pu-contaminated wound were analyzed using Markov Chain Monte Carlo (MCMC) to obtain the posterior distribution of the intakes and doses. An empirical approach was used to model the effects of medical treatments (chelation and excision) on the reduction of doses. It was calculated that DTPA enhanced the urinary excretion, on average, by a factor of 17. The empirical analysis also allowed calculation of the efficacies of the medical treatments-excision and chelation averted approximately 76% and 5.5%, respectively, of the doses that would have been if there were no medical treatment. All bioassay data are provided in the appendix for independent analysis and to facilitate the compartmental modeling approaches being developed by the health physics community.

Development of a New Chelation Model: Bioassay Data Interpretation and Dose Assessment after Plutonium Intake via Wound and Treatment with DTPA.

The administration of chelation therapy to treat significant intakes of actinides, such as plutonium, affects the actinide's normal biokinetics. In particular, it enhances the actinide's rate of excretion, such that the standard biokinetic models cannot be applied directly to the chelation-affected bioassay data in order to estimate the intake and assess the radiation dose. The present study proposes a new chelation model that can be applied to the chelation-affected bioassay data after plutonium intake via wound and treatment with DTPA. In the proposed model, chelation is assumed to occur in the blood, liver, and parts of the skeleton. Ten datasets, consisting of measurements of C-DTPA, Pu, and Pu involving humans given radiolabeled DTPA and humans occupationally exposed to plutonium via wound and treated with chelation therapy, were used for model development. The combined dataset consisted of daily and cumulative excretion (urine and feces), wound counts, measurements of excised tissue, blood, and post-mortem tissue analyses of liver and skeleton. The combined data were simultaneously fit using the chelation model linked with a plutonium systemic model, which was linked to an ad hoc wound model. The proposed chelation model was used for dose assessment of the wound cases used in this study.

USTUR Special Session Roundtable-US Transuranium and Uranium Registries (USTUR): A Five-decade Follow-up of Plutonium and Uranium Workers.

The US Transuranium and Uranium Registries is a human tissue program that collects tissues posthumously from former nuclear workers and radiochemically analyzes them for actinides such as plutonium, americium, and uranium. It was established in 1968 with the goal of advancing science and improving the safety of future workers. Roundtable participants recalled various aspects of this multidisciplinary research program, from establishing consistent autopsy protocols to comparing the registries' findings to those of other programs, such as the historical beagle dog studies and the Russian Radiobiological Human Tissue Repository. The importance of meeting ethical and legal requirements, including written consent forms, was emphasized, as was the need to know whether workers were exposed to nonradiological hazards such as beryllium or asbestos. At Rocky Flats, a bioassay program was established to follow workers after they terminated employment. The resulting data continue to help researchers to improve the biokinetic models that are used to estimate intakes and radiation doses. After 50 y, the US Transuranium and Uranium Registries continues to contribute to our understanding of actinides in humans, which is a testament to the vision of its founders, the generosity of its tissue donors, and the many dedicated scientists who have worked together to achieve a common goal.

Rapid Response, Dose Assessment, and Clinical Management of a Plutonium-contaminated Puncture Wound.

Internalization of radionuclides occurs not only by inhalation, ingestion, parenteral injection (i.e., administration of radioactive material for a medical purpose), and direct transdermal absorption, but also by contaminated wounds. In June 2010, a glove-box operator at the U.S. Department of Energy's Savannah River Site sustained a puncture wound while venting canisters containing legacy materials contaminated with Pu. To indicate the canisters had been vented, a flag was inserted into the vent hole. The shaft of the flag penetrated the protective gloves worn by the operator. Initial monitoring performed with a zinc-sulfide alpha detector indicated 300 dpm at the wound site. After being cleared by radiological controls personnel, the patient was taken to the site medical facility where decontamination was attempted and diethylenetriaminepentaacetic acid (DTPA) was administered intravenously within 1.5 h of the incident. The patient was then taken to the Savannah River Site In Vivo Counting Facility where the wound was counted with a Canberra GL 2820 high-purity germanium detector, capable of quantifying contamination by detecting low-energy x rays and gamma rays. In addition to the classic 13, 17, and 20 keV photons associated with Pu, the low-yield (0.04%) 43.5 keV peak was also detected. This indicated a level of wound contamination orders of magnitude above the initial estimate of 300 dpm detected with handheld instrumentation. Trace quantities of Am were also identified via the 59.5 keV peak. A 24 h urine sample collection was begun on day 1 and continued at varying intervals for over a year. The patient underwent a punch biopsy at 3 h postincident (14,000 dpm removed) and excisional biopsies on days 1 and 9 (removal of an additional 3,200 dpm and 3,800 dpm, respectively). The initial post-DTPA urine sample analysis report indicated excretion in excess of 24,000 dpm Pu. Wound mapping was performed in an effort to determine migration from the wound site and indicated minimum local migration. In vivo counts were performed on the liver, axillary lymph nodes, supratrochlear lymph nodes, and skeleton to assess uptake and did not indicate measurable activity. Seventy-one total doses of DTPA were administered at varying frequencies for 317 d post intake. After allowing 100 d for removal of DTPA from the body, five 24 h urine samples were collected and analyzed for dose assessment by using the wound model described in National Council on Radiation Protection and Measurements Report No. 156. The total effective dose averted via physical removal of the contaminant and DTPA administration exceeded 1 Sv, demonstrating that rapid recognition of incident magnitude and prompt medical intervention are critical for dose aversion.

Risk of Lung Cancer Mortality in Nuclear Workers from Internal Exposure to Alpha Particle-emitting Radionuclides.

BACKGROUND: Carcinogenic risks of internal exposures to alpha-emitters (except radon) are poorly understood. Since exposure to alpha particles-particularly through inhalation-occurs in a range of settings, understanding consequent risks is a public health priority. We aimed to quantify dose-response relationships between lung dose from alpha-emitters and lung cancer in nuclear workers. METHODS: We conducted a case-control study, nested within Belgian, French, and UK cohorts of uranium and plutonium workers. Cases were workers who died from lung cancer; one to three controls were matched to each. Lung doses from alpha-emitters were assessed using bioassay data. We estimated excess odds ratio (OR) of lung cancer per gray (Gy) of lung dose. RESULTS: The study comprised 553 cases and 1,333 controls. Median positive total alpha lung dose was 2.42 mGy (mean: 8.13 mGy; maximum: 316 mGy); for plutonium the median was 1.27 mGy and for uranium 2.17 mGy. Excess OR/Gy (90% confidence interval)-adjusted for external radiation, socioeconomic status, and smoking-was 11 (2.6, 24) for total alpha dose, 50 (17, 106) for plutonium, and 5.3 (-1.9, 18) for uranium. CONCLUSIONS: We found strong evidence for associations between low doses from alpha-emitters and lung cancer risk. The excess OR/Gy was greater for plutonium than uranium, though confidence intervals overlap. Risk estimates were similar to those estimated previously in plutonium workers, and in uranium miners exposed to radon and its progeny. Expressed as risk/equivalent dose in sieverts (Sv), our estimates are somewhat larger than but consistent with those for atomic bomb survivors.See video abstract at, http://links.lww.com/EDE/B232.

Medical Effects of a Transuranic "Dirty Bomb".

The modern military battlefields are characterized by the use of nonconventional weapons such as encountered in the conflicts of the Gulf War I and Gulf War II. Recent warfare in Iraq, Afghanistan, and the Balkans has introduced radioactive weapons to the modern war zone scenarios. This presents the military medicine with a new area of radioactive warfare with the potential large scale contamination of military and civilian targets with the variety of radioactive isotopes further enhanced by the clandestine use of radioactive materials in the terrorist radioactive warfare. Radioactive dispersal devices (RDDs), including the "dirty bomb," involve the use of organotropic radioisotopes such as iodine 131, cesium 137, strontium 90, and transuranic elements. Some of the current studies of RDDs involve large-scale medical effects, social and economic disruption of the society, logistics of casualty management, cleanup, and transportation preparedness, still insufficiently addressed by the environmental and mass casualty medicine. The consequences of a dirty bomb, particularly in the terrorist use in urban areas, are a subject of international studies of multiple agencies involved in the management of disaster medicine. The long-term somatic and genetic impact of some from among over 400 radioisotopes released in the nuclear fission include somatic and transgenerational genetic effects with the potential challenges of the genomic stability of the biosphere. The global contamination is additionally heightened by the presence of transuranic elements in the modern warzone, including depleted uranium recently found to contain plutonium 239, possibly the most dangerous substance known to man with one pound of plutonium capable of causing 8 billion cancers. The planning for the consequences of radioactive dirty bomb are being currently studied in reference to the alkaline earths, osteotropic, and stem cell hazards of internally deposited radioactive isotopes, in particular uranium and transuranic elements. The spread of radioactive materials in the area of the impact would expose both military and civilian personnel to the blast and dust with both inhalational, somatic, and gastrointestinal exposure, in the aftermath of the deployment of RDDs. The quantities of radioactive materials have proliferated from the original quantity of plutonium first isolated in 1941 from 0.5 mg to the current tens of thousands of kilograms in the strategic nuclear arsenal with the obvious potential consequences to the biosphere and mankind. In an event of RDD employment, the immediate goal of disaster and mass casualty medicine would be a synchronized effort to contain the scope of the event, followed by cleanup and treatment procedures. A pragmatic approach to this problem is not always possible because of unpredictability of the terrorist-use scenarios.

Doses and lung cancer risks from exposure to radon and plutonium.

PURPOSE: Epidemiological studies of the French uranium miners and the plutonium workers at the Mayak nuclear facility have provided excess relative risk (ERR) estimates per unit absorbed lung dose from alpha radiation. The aim of this paper was to review these two studies and to derive values of the relative biological effectiveness (RBE) of alpha particles for the induction of lung cancer. MATERIALS AND METHODS: We examined and compared the dosimetry assumptions and methodology used in the epidemiological studies of uranium miners and the plutonium workers. Values of RBE were obtained by comparing risk coefficients including comparison of lifetime risks for a given population. To do this, preliminary calculations of lifetime risks following inhalation of plutonium were carried out. RESULTS AND CONCLUSIONS: Published values of risk per unit dose following inhalation of radon progeny and plutonium were in agreement despite the very different dose distributions within the lungs and the different ways the doses were calculated. Values of RBE around 10-20 were obtained by comparing ERR values, but with wide uncertainty ranges. Comparing lifetime risks gave similar values (10, 19 and 21). This supports the use of a radiation weighting factor of 20 for alpha particles for radiation protection purposes.

(238)Pu elimination profiles after delayed treatment with 3,4,3LI(1,2HOPO) in female and male Swiss-Webster mice.

PURPOSE: To characterize the dose-dependent and sex-related efficacy of the hydroxypyridinonate decorporation agent 3,4,3-LI(1,2-HOPO) at enhancing plutonium elimination when post-exposure treatment is delayed. MATERIALS AND METHODS: Six parenteral dose levels of 3,4,3-LI(1,2-HOPO) from 1-300 µmol/kg were evaluated for decorporating plutonium in female and male Swiss-Webster mice administered a soluble citrate complex of (238)Pu and treated 24 hours later. Necropsies were scheduled at four time-points (2, 4, 8, and 15 days post-contamination) for the female groups and at three time-points (2, 4, and 8 days post-contamination) for the male groups. RESULTS: Elimination enhancement was dose-dependent in the 1-100 µmol/kg dose range at all necropsy time-points, with some significant reductions in full body and tissue content for both female and male animals. The highest dose level resulted in slight toxicity, with a short recovery period, which delayed excretion of the radionuclide. CONCLUSIONS: While differences were noted between the female and male cohorts in efficacy range and recovery times, all groups displayed sustained dose-dependent (238)Pu elimination enhancement after delayed parenteral treatment with 3,4,3-LI(1,2-HOPO), the actinide decorporation agent under development.

Developing a physiologically based approach for modeling plutonium decorporation therapy with DTPA.

PURPOSE: To develop a physiologically based compartmental approach for modeling plutonium decorporation therapy with the chelating agent Diethylenetriaminepentaacetic acid (Ca-DTPA/Zn-DTPA). MATERIALS AND METHODS: Model calculations were performed using the software package SAAM II (©The Epsilon Group, Charlottesville, Virginia, USA). The Luciani/Polig compartmental model with age-dependent description of the bone recycling processes was used for the biokinetics of plutonium. RESULTS: The Luciani/Polig model was slightly modified in order to account for the speciation of plutonium in blood and for the different affinities for DTPA of the present chemical species. The introduction of two separate blood compartments, describing low-molecular-weight complexes of plutonium (Pu-LW) and transferrin-bound plutonium (Pu-Tf), respectively, and one additional compartment describing plutonium in the interstitial fluids was performed successfully. CONCLUSIONS: The next step of the work is the modeling of the chelation process, coupling the physiologically modified structure with the biokinetic model for DTPA. RESULTS of animal studies performed under controlled conditions will enable to better understand the principles of the involved mechanisms.

Dose-dependent analysis of acute medical effects of mixed neutron-gamma radiation from selected severe 235U or 239Pu criticality accidents in USSR, United States, and Argentina.

Eight of the most severe cases of acute radiation disease (ARS) known to have occurred in humans (as the result of criticality accidents) had survival times less than 120 h (herein defined as "early death"). These accidents were analyzed and are discussed with respect to the specific accident scenarios and the resulting accident-specific, mixed neutron-gamma radiation clinical dose distributions. This analysis concludes that the cardiovascular system appears to be the most critical organ system failure for causing "early death" following approximate total body, mixed gamma-neutron radiation doses greater than 40-50 Gy. The clinical data also suggest that there was definite chest dose dependence in the resulting survival times for these eight workers, who unfortunately suffered profound radiation injury and unusual clinical effects from such high dose radiation exposures. In addition, "toxemic syndrome" is correlated with the irradiation of large volumes of soft tissues. Doses to the hands or legs greater than 80-100 Gy or radiation lung injury also play significant but secondary roles in causing "early death" in accidents delivering chest doses greater than 50 Gy.

Twenty-four years of follow-up for a Hanford plutonium wound case.

A 1985 plutonium puncture wound resulted in the initial deposition of 48 kBq of transuranic alpha activity, primarily 239+240Pu and 241Am, in a worker's right index finger. Surgical excisions in the week following reduced the long-term residual wound activity to 5.4 kBq, and 164 DTPA chelation therapy administrations over 17 mo resulted in urinary excretion of about 7 kBq. The case was published in 1988, but now 24 y of follow-up data are available. Annual bioassays have included in-vivo measurements of 241Am in the wound, skeleton, liver, lung, and axillary lymph nodes, and urinalyses for plutonium and 241Am. These measurements have shown relatively stable levels of 241Am at the wound site, with gradually increasing amounts of 241Am detected in the skeleton. Liver measurements have shown erratic detection of 241Am, and the lung measurements indicate Am but as interference from activity in the axillary lymph nodes and skeleton rather than activity in the lung. Urine excretion of Pu since termination of chelation therapy has typically ranged from 10 to 20 mBq d, with Am excretion about 10% of that for 239+240Pu. Annual routine medical exams have not identified any adverse health effects associated with the intake.

Cancer incidence in municipalities near two former nuclear materials processing facilities in Pennsylvania--an update.

Previous studies of cancer incidence among persons living in municipalities within one mile of two nuclear materials processing and fabrication plants in Pennsylvania were extended for the years 1998-2004. It had been shown that mailing addresses for residents of rural areas often did not reflect the actual municipality of residence and, if not corrected, would bias study results. The previous studies had corrected for this bias. Accordingly for the extended study, we obtained mailing addresses from the Pennsylvania Department of Health (PDH) for 866 persons with cancer who presumably lived in one of eight minor civil divisions (MCDs) near or encompassing the former nuclear facilities, designated as Area 1 in previous studies conducted by the PDH. Street addresses were geocoded and local postmasters were asked to place rural delivery addresses, post office boxes and street addresses that could not be geocoded into the correct MCD of actual residence. Over 15% of the mailing addresses were found not to be within the boundaries of the Area 1 municipalities. After the mailing addresses of individuals with cancer were placed in their proper MCD of residence, the number of persons diagnosed with cancer (n = 708) and confirmed to have lived in Area 1 was as expected (728.4) based on cancer incidence rates in the general population of Pennsylvania (SIR 0.97; 95% CI 0.90-1.05). To further evaluate the patterns of cancer rates near these nuclear facilities and the influence of improved reporting and geocoding of addresses over time, analyses were conducted of publicly available cancer incidence data from 1990 through 2004. Based on mailing addresses, a steady decrease in the number of cancers reported in the Area 1 proximal MCDs was seen, in contrast to a steady rise in the number of cancers reported in seven adjacent but more distant MCDs from the nuclear facilities, designated as Area 2. These patterns were attributed to improvements over time in the geocoding of residential mailing addresses coupled with the gradual elimination and replacement of rural delivery addresses with street addresses. The incorrect placement of mailing addresses in residential Area 1 municipalities prior to about 2002 overestimated the number of cancers occurring among residents living in close proximity to the nuclear facilities and, correspondingly, underestimated the number among Area 2 residents. Summing Area 1 and Area 2 data showed that there was no change in cancer rates over time. These results are consistent with previous studies indicating that living in municipalities near the former Apollo-Parks nuclear facilities was not associated with an increase in cancer occurrence.

To recycle or not to recycle? An intergenerational approach to nuclear fuel cycles.

This paper approaches the choice between the open and closed nuclear fuel cycles as a matter of intergenerational justice, by revealing the value conflicts in the production of nuclear energy. The closed fuel cycle improve sustainability in terms of the supply certainty of uranium and involves less long-term radiological risks and proliferation concerns. However, it compromises short-term public health and safety and security, due to the separation of plutonium. The trade-offs in nuclear energy are reducible to a chief trade-off between the present and the future. To what extent should we take care of our produced nuclear waste and to what extent should we accept additional risks to the present generation, in order to diminish the exposure of future generation to those risks? The advocates of the open fuel cycle should explain why they are willing to transfer all the risks for a very long period of time (200,000 years) to future generations. In addition, supporters of the closed fuel cycle should underpin their acceptance of additional risks to the present generation and make the actual reduction of risk to the future plausible.

[Chronic radiation damage by uranium and plutonium nuclear fission products].

Chronical radiation sickness is a special form of the radiation damage. It occurs when doses of chronical irradiation exceed their values established for professionals. The sickness is well studied in clinical observations. It may take place also if uranium and plutonium nuclear fission products (NFP) enter the organism. In the last case the chronical radiation sickness practically is not investigated. In the article we present the results of the experimental studies on dogs of the damage caused by NFP.

El cáncer en la Comarca de las Cinco Villas (Zaragoza)

Fundamento: Conocer la tasa de incidencia del cáncer en la comarca de las Cinco Villas, y analizar si es superior a la de otras zonas. Sujetos y métodos: Se ha utilizado como material los casos de pacientes diagnosticados con cáncer que pertenecen a la comarca de estudio recogidos en los hospitales de referencia de la zona. Los casos obtenidos son 400 casos de cáncer que han debutado en los años en que se centra el estudio, 1997, 1998 y 1999. El método usado ha sido el epidemiológico descriptivo. Se han calculado las tasas de incidencia por grupos de edad y por años de estudio, las tasas ajustadas a la población mundial por 100.000 habitantes, los límites de confianza y el riesgo relativo. Resultados: Las tasas ajustadas obtenidas han sido de 218,6, I.C.ñ25,46, para mujeres de 172,4, I.C.ñ34,92, y para hombres de 272,9, I.C.ñ37,85. Los riesgos relativos han sido en hombres de 0,72, (LC: 0,03-1,72,) y en mujeres de 0,86, (LC: 0,03-1,2.). Conclusiones: No se ha encontrado en esta zona aumentos estadísticamente significativos ni en las tasas ajustadas, ni en el riesgo relativo (AU)

Plutonium and other alpha emitters in mushrooms from Poland, Spain and Ukraine.

The paper presents results on Pu, U and Th isotope activity concentration measurements in some mushroom samples collected in Poland, Spain and Ukraine. The sampling sites differ a lot with regard to observed levels of Pu, its origin and isotope ratios as well as the environmental properties. Some of the Polish samples were collected in the northeastern part of the country with up to 30 Bq/m2 of Chernobyl Pu deposition. Other Polish and the Spanish samples are from areas with almost exclusively global fallout Pu present. Ukrainian samples were collected in a highly contaminated area with a deposition of about 3.7 kBq/m2 of Chernobyl (239-240)Pu. The maximum (239+240)Pu activity concentration was found equal to (54+/-4) Bq/kg (dw--dry weight) for a Ukrainian Cantharellus cibarius sample. Ukrainian samples have an extremely high radiocesium level, with maximum of (51+/-4) MBq/kg (dw). The maximum (239+240)Pu activity concentration for Polish samples was (81+/-5) mBq/kg (dw) for Xerocomus badius. From the isotopic ratio in this sample it can be concluded that Chernobyl fallout is the origin of Pu. More than twice as large was the Spanish maximum for Hebeloma cylindrosporum but with only global fallout Pu. Some aspects of the transfer of nuclides to fruit bodies is discussed and in some cases the transfer factors or aggregation coefficients were calculated. Especially high transfer factors were found for Hebeloma cylindrosporum from Spain.